Cell

Cell

Volume 79, Issue 5, 2 December 1994, Pages 755-765
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Article
Behavioral and anatomical deficits in mice homozygous for a modified β-amyloid precursor protein gene

https://doi.org/10.1016/0092-8674(94)90066-3Get rights and content

Abstract

The β-amyloid precursor protein (βAPP) gene of the mouse was disrupted by inserting into exon 2 a cassette containing a neomycin resistance gene and a putative transcription termination sequence. Contrary to expectation, brain and other tissues from mice homozygous for the insertion still contained βAPP-specific RNA, albeit at a level 5- to 10-fold lower than wild type and lacking the disrupted exon, which had been spliced out. The brain contained shortened βAPP-specific protein at a low level. Mutant mice were severely impaired in spatial learning and exploratory behavior and showed increased incidence of agenesis of the corpus callosum.

References (55)

  • M.P. Mattson et al.

    Evidence for excitoprotective and intraneuronal calcium-regulating roles for secreted forms of the β-amyloid precursor protein

    Neuron

    (1993)
  • A.P. McMahon et al.

    The Wnt-1 (int-1) protooncogene is required for development of a large region of the mouse brain

    Cell

    (1990)
  • D. Montag et al.

    Mice deficient for the myelin associated glycoprotein show subtle abnormalities in myelin

    Neuron

    (1994)
  • R.G.M. Morris

    Developments of a water-maze procedure for studying spatial learning in the rat

    J. Neurosci. Meth.

    (1984)
  • S. Noguchi et al.

    Apolipoprotein E genotype and Alzheimer's disease

    Lancet

    (1993)
  • D.J. Selkoe

    Physiological production of the β-amyloid protein and the mechanism of Alzheimer's disease

    Trends Neurosci.

    (1993)
  • H.H. Slunt et al.

    Expression of a ubiquitous, cross-reactive homologue of the mouse beta-amyloid precursor protein (APP)

    J. Biol. Chem.

    (1994)
  • P. Soriano et al.

    Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice

    Cell

    (1991)
  • K.R. Thomas et al.

    Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells

    Cell

    (1987)
  • J.M. Wehner et al.

    Hippocampal protein kinase C activity is reduced in poor spatial learners

    Brain Res.

    (1990)
  • D.P. Wolfer et al.

    A computer program for detailed off-line analysis of Morris water maze behaviour

    J. Neurosci. Meth.

    (1992)
  • T. Yamada et al.

    complementary DNA for the mouse homolog of the human amyloid beta protein precursor

    Biochem. Biophys. Res. Commun.

    (1987)
  • T. Yamada et al.

    Structure and expression of the alternatively-spliced forms of mRNA for the mouse homolog of Alzheimer's disease amyloid beta protein precursor

    Biochem. Biophys. Res. Commun.

    (1989)
  • S. Yoshikai et al.

    Genomic organization of the human amyloid beta-protein precursor gene

    Gene

    (1990)
  • S. Bernasconi-Guastalla et al.

    Hippocampal mossy fibers and swimming navigation in mice: correlations with size and left-right asymmetries

    Hippocampus

    (1994)
  • K. Beyreuther et al.

    Mechanisms of amyloid deposition in Alzheimer's disease

    Ann. NY Acad. Sci.

    (1991)
  • H. Büeler et al.

    Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein

    Nature

    (1992)

    • Cited by (0)

    †

    The first two authors contributed equally to this work.

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